(d,l)2-Mercaptomethyl-5-guanidinopentanoic acid is reported as a potent inhibitor of carboxypeptidase B [Ondetti, M. A., Condon, M. E., Reid, J., Sabo, E. F., Cheung, H. S., and Cushman, D. W., Biochemistry 18, 1427-1430 (1979)]. More recently, this compound has been shown to have excellent activity in inhibiting serum carboxypeptidase N (SCPN) [Hugli, T. E., Gerard, C., Kawahara, M., Scheetz, M. E., Barton, R., Briggs, S., Koppel, G., and Russell, S., Molecular and Cellular Biochemistry 41, 59-66 (1981)].
Ondetti et al, supra, details a multi-step sequence for the preparation of (d,l)2-mercaptomethyl-5-guanidinopentanoic acid. It is to a modification of the described method of preparation that this invention is directed. In the sequence described by Ondetti et al., supra, an intermediate, 2-acetylthiomethyl-5-guanidinopentanoic acid, is prepared by treating the corresponding 5-amino compound with 1-guanyl-3,5-dimethylpyrazole nitrate in dry N,N-dimethylformamide. After an extended period of reaction, only minor levels of conversion are experienced. It has now been discovered that the levels of conversion to the guanidino compound can be substantially increased and the reaction time substantially shortened by carrying out the reaction in accordance with the process of this invention.